The overall objective is to understand collagen metabolism in normal and abnormal wound healing so that human diseases characterized by excessive scar formation (excessive collagen deposition) or inadequate wound strength (inadequate collagen deposition) can be corrected by regulation of collagen metabolism. An animal model for excessive collagen deposition does not exist. However, the human keloid serves as a model in which the equilibrium between collagen synthesis and degradation has been lost resulting in overabundant collagen deposition. In contrast, human cutaneous striae may be a model of insufficient or abnormal collagen deposition. Hypotheses formulated from keloid and other human wounds are tested in cell culture systems, rat wound models and chicken tendon models to clarify events in normal and abnormal healing. Having found that collagen synthesis in keloids and keloid-derived fibroblasts is greater than normal skin and normal scar controls, keloid fibroblasts will be further characterized to study the effects of pharmacologic agents, and epithelial and inflammatory cell interactions on keloid collagen metabolism. Monoclonal and immunologic studies of these abnormal lesions will be continued to determine the etiology of abnormal repair. Parallel animal and cell culture studies will examine the role of inflammatory cells (marcophage) and anti-inflammatory drugs (corticosteroids, indomethacin) on collagen metabolism. Because collagen Types appear to relate to structure and function, potential Type alterations with pharmacologic agents and mechanical forces (striae and chicken tendon model) will be studied. New methodologies (i.e., stable proline isotopes) will be developed for future in vivo human wound healing studies.